Nipple smear cytology is of no value in the management of women with nipple discharge.

Nipple smear cytology (NSC) is commonly used in the management of patients with nipple discharge. A retrospective review was conducted to evaluate the results of NSC and determine if the test provided important information that potentially altered patient management. Two hundred twenty-two NSC specimens were obtained from 165 patients. No malignant cytologic diagnoses were made. Four patients were subsequently shown to have cancer. Three patients with cancer had negative NSC. All four cancers were detected as a result of surgical biopsies directed at associated clinical or imaging findings. In many instances the results of NSC, negative or abnormal, did not affect the subsequent management of these patients. The total cost of performing these tests was approximately $12,000. NSC is neither helpful nor useful in the management of patients with nipple discharge.

13-year outcomes following treatment for clinically localized prostate cancer in a population based cohort.

PURPOSE: Because data from randomized trials initiated after the introduction of prostate specific antigen testing are unavailable, we performed a retrospective, population based study to estimate prostate cancer specific survival and overall survival after surgery, radiation or observation to manage clinically localized prostate cancer. MATERIALS AND METHODS: From the Connecticut Tumor Registry we identified Connecticut residents 75 years or younger diagnosed with clinically localized prostate cancer between January 1, 1990 and December 31, 1992. We obtained information from physician offices concerning treatments received by 1,618 patients who underwent surgery (802), external beam radiation therapy (702) or no initial therapy (114) and subsequent medical outcomes. Treatment comparisons were adjusted for pretreatment Gleason score, prostate specific antigen and clinical stage along with age at diagnosis and comorbidities using 3 methods, including categorization by risk, a proportional hazards model and a propensity score. RESULTS: At an average followup of 13.3 years 13% of patients had died of prostate cancer, 5% had died of other cancers and 24% had died other noncancer causes. Patients undergoing surgery were younger, and had more favorable histology and lower pretreatment prostate specific antigen compared to patients undergoing radiation. Patients who elected observation had significantly worse cause specific survival than those who elected surgery. They also fared worse than men who received radiation therapy but the difference was not statistically significant, possibly because of the small number of prostate cancer deaths to date. CONCLUSIONS: Our findings suggest that patients undergoing surgery for clinically localized prostate cancer may have a cancer specific survival advantage compared to those electing radiation or observation. However, only a randomized trial can control for the many known and unknown confounding factors that can affect long-term outcomes.

Prostate cancer and the Will Rogers phenomenon.

BACKGROUND: Information on tumor stage and grade are used to assess cancer prognosis and to produce standardized comparisons of end results over time. Changes in the interpretation of classification schemes can alter the apparent distribution of cancer stage or grade in the absence of a true biologic change. Since the introduction of prostate-specific antigen testing, the reported incidence of low-grade prostate cancer has declined. To determine whether this decline is in part a result of Gleason score reclassification during the same time period, we documented the potential impact of reclassification between 1992 and 2002 on clinical outcomes. METHODS: A population-based cohort of 1858 men who were < or = 75 years of age at diagnosis of prostate cancer in 1990-1992 was assembled retrospectively from the Connecticut Tumor Registry. Histology slides of the diagnostic prostate tissue were retrieved and reread in 2002-2004 by an experienced pathologist blinded to the original Gleason score readings. Prostate cancer mortality rates for the cohort calculated using the original Gleason score readings were compared with those calculated using the contemporary Gleason score readings. Statistical tests were two sided. RESULTS: The contemporary Gleason score readings were statistically significantly higher than the original readings (mean score increased from 5.95 to 6.8; difference = 0.85, 95% confidence interval = 0.79 to 0.91; P < .001). Consequently, the Gleason score-standardized contemporary prostate cancer mortality rate (1.50 deaths per 100 person-years) appeared to be 28% lower than standardized historical rates (2.08 deaths per 100 person-years), even though the overall outcome was unchanged. This apparent improvement in mortality held for all Gleason score categories. CONCLUSIONS: In this population, a decline in the reported incidence of low-grade prostate cancers appears to be the result of Gleason score reclassification over the past decade. This reclassification resulted in apparent improvement in clinical outcomes. This finding reflects a statistical artifact known as the Will Rogers phenomenon.

The interleukin-1 family of cytokines and receptors in human breast cancer: implications for tumor progression.

We have previously described the expression of interleukin cytokines (IL)-1alpha, IL-1beta, and IL-1 receptor antagonist (IL-1ra) in human breast cancer (HBC) tissue. Based on our previous studies, we hypothesize that the IL-1 family of cytokines, antagonists (IL-1ra) and receptors (IL-1RI and IL-1RII) are present within the human breast cancer (HBC) tumor microenvironment and that the IL-1 network of cytokines and receptors within the tumor microenvironment can control tumor cell subpopulation expression of other protumorigenic cytokines such as the angiogenic/growth factor, interleukin-8 (IL-8). To test this hypothesis we characterized the in vivo expression of the IL-1 network in HBC tissues and homogenates by immunohistochemistry (IHC) and ELISA. Additionally, we examined IL-1R expression in HBC cell lines in vitro and in a murine xenograft model by IHC. Finally, we determined the ability of IL-1 to induce IL-8 expression in in vitro using HBC cell lines. We observed that not only are the IL-1 cytokines present in HBC tissue and homogenates, but that IL-1Rs and IL-8 are also present in the HBC tumor microenvironment. Additionally, expression levels for some members of the IL-1/IL-8 network of cytokines correlated with the prognostic indicators, ER/PR. Using HBC cell lines, we observed that HBC cell lines express IL-1Rs in vitro and in the xenograft model. Furthermore, in vitro, HBC cell lines show a spectrum of responsiveness to IL-1 as measured by expression the proangiogenic/mitogenic cytokine IL-8. Our data clearly demonstrate the presence and distribution of IL-1 cytokines and receptors in HBC and suggests that the local expression of IL-1 results in the activation of a population of cells within the HBC tumor microenvironment. This activation of the IL-1/IL-1R cytokine family via autocrine and/or paracrine mechanisms leads to a cascade of secondary protumorigenic cytokines. These secondary signals induce the expression of numerous protumorigenic activities such as the expression of IL-8, and subsequently contribute to angiogenesis, tumor proliferation, and tumor invasion.

Human Liver Neoplasia and Steroid Exposure.

This study examines experience with over 250 liver tumors in young women. Most were oral contraceptive related. There were two distinct benign liver tumor types: focal nodular hyperplasia and liver cell adenoma. Six benign liver tumors were examined for estrogen receptors. They did not contain significant quantities of estrogen receptor, supporting experimental studies of an epigenetic origin. Multiple tumors occurred in about 20% of cases but did not change the favorable prognosis associated with benign tumors. The most significant source of morbidity and mortality was spontaneous hemorrhage or rupture. Twenty-three women in this series had hepatocellular carcinoma and the majority of these were associated with prolonged steroid usage. These malignant liver tumors occurred in young females without cirrhosis or other factors known to be associated with hepatic malignancy. Unlike "hepatocellular carcinomas" reported in males taking anabolic androgenic steroids, the tumors in females had a high rate of metastasis to a variety of organs. The risk of liver tumors in oral contraceptive users remains unknown, but must be very small since an estimated 150 million women worldwide and 40 million in the U.S.A. have used oral contraceptives.